Trifluoroacetylation of amino acids and amines has been used as a method of protecting the amino group in chemical reactions. For example, trifluoroacetic anhydride has been used as a trifluoroacetylation reagent of amino acids. However, this reagent has been found to have the following drawbacks: (1) its high reactivity limited its use, (2) it has some unfavorable solubility characteristics, (3) the formation of unsymmetrical anhydrides occurs, and (4) racemization of chiral centers occurs.
The S-ethyl trifluorothioacetate reagent disclosed in Schallenberg et al., J. Am. Chem. Soc. 1955, 77, 2779, and in Hauptschein, M., Stokes, C. S., Nodiff, E. A. J. Am. Chem. Soc. 1952, 74, 4005 overcame all of these disadvantages. However, it introduced a new drawback, the formation of a disagreeable odoriferous by-product.
Alkyl trifluoroacetates have also been used as trifluoroacetylation reagents as disclosed in, for example, Bayer et al., J. Am. Chem. Soc. 1972, 94, 265. The alkyl trifluoroacetates, however, are used in excess and are sensitive to hydrolysis, resulting in deterioration during handling and storage.
Solid phase synthesis and the use of polymer supported reactions in organic synthesis has been explored in the prior art. See, for example, Polymer-supported Reactions in Organic Synthesis (P. Hodge and D. C. Sherrington ed. 1980), especially pages 136-139. Other examples of polymer-bound reagents are disclosed in Dixit, D. M. and Leznoff C. C., Israel Journal of Chemistry 1978, 17, 248; Frechet, J. M. J., Tetrahedron 1981, 37, 663; Crowley, J. I., and Rapoport, H., Acc. Chem. Res. 1976, 9, 135; Mohanraj, S., Ford, W. T., J. Org. Chem. 1985, 50, 1616; and Chiu, S. L. and Anderson L., Carbohydrate Research 1976, 50, 227. None of these references, however, disclose or suggest the present invention.